Authors
Ana Ortega-Molina, Isaac W Boss, Andres Canela, Heng Pan, Yanwen Jiang, Chunying Zhao, Man Jiang, Deqing Hu, Xabier Agirre, Itamar Niesvizky, Ji-Eun Lee, Hua-Tang Chen, Daisuke Ennishi, David W Scott, Anja Mottok, Christoffer Hother, Shichong Liu, Xing-Jun Cao, Wayne Tam, Rita Shaknovich, Benjamin A Garcia, Randy D Gascoyne, Kai Ge, Ali Shilatifard, Olivier Elemento, Andre Nussenzweig, Ari M Melnick, Hans-Guido Wendel
Publication date
2015/10
Journal
Nature medicine
Volume
21
Issue
10
Pages
1199-1208
Publisher
Nature Publishing Group US
Description
The gene encoding the lysine-specific histone methyltransferase KMT2D has emerged as one of the most frequently mutated genes in follicular lymphoma and diffuse large B cell lymphoma; however, the biological consequences of KMT2D mutations on lymphoma development are not known. Here we show that KMT2D functions as a bona fide tumor suppressor and that its genetic ablation in B cells promotes lymphoma development in mice. KMT2D deficiency also delays germinal center involution and impedes B cell differentiation and class switch recombination. Integrative genomic analyses indicate that KMT2D affects methylation of lysine 4 on histone H3 (H3K4) and expression of a set of genes, including those in the CD40, JAK-STAT, Toll-like receptor and B cell receptor signaling pathways. Notably, other KMT2D target genes include frequently mutated tumor suppressor genes such as TNFAIP3, SOCS3 and …
Scholar articles
A Ortega-Molina, IW Boss, A Canela, H Pan, Y Jiang… - Nature medicine, 2015